Can fortified foods and snacks increase the energy and protein intake of hospitalised older patients? A systematic review.

BACKGROUND: Undernutrition affects over 44% of hospitalised older people, who often dislike oral nutritional supplements (ONS). This review summarises the evidence for an alternative strategy, using energy and protein dense meals (via fortification) or snacks (supplementation) to increase the dietary energy and protein intake of older inpatients. METHODS: A search was conducted through PubMed, EMBASE, CINAHL and the Cochrane database of systematic reviews (May 1996 to May 2016) that used fortification or supplementation to increase the energy or protein intake of patients (mean age ≥60 years) in hospitals or rehabilitation centres. RESULTS: Ten articles (546 patients, mean age 60-83 years) were identified. Compared with usual nutritional care, six studies using either energy or protein based fortification and supplementation significantly increased intake of energy (250-450 kcal day-1 ) or protein (12-16 g day-1 ). Two studies enriched menus with both energy and protein, and significantly increased both energy (698 kcal day-1 and 21 kJ kg-1 ) and protein (16 g and 0.2 g kg-1 ) intake compared to usual care. ONS was similar to supplementation in one study but superior to fortification in another. Four studies reported good acceptability of enriched products and two studies that found they were cost-effective. CONCLUSIONS: Compared with usual nutritional care, energy- and protein-based fortification and supplementation could be employed as an effective, well-tolerated and cost-effective intervention to improve dietary intake amongst older inpatients. This strategy may be particularly useful for patients with cognitive impairment who struggle with ONS, and clinical trials are required to compare these approaches and establish their impact on functional outcomes.

Effect of sulphation on the oestrogen agonist activity of the phytoestrogens genistein and daidzein in MCF-7 human breast cancer cells.

The phytoestrogens genistein, daidzein and the daidzein metabolite equol have been shown previously to possess oestrogen agonist activity. However, following consumption of soya diets, they are found in the body not only as aglycones but also as metabolites conjugated at their 4'- and 7-hydroxyl groups with sulphate. This paper describes the effects of monosulphation on the oestrogen agonist properties of these three phytoestrogens in MCF-7 human breast cancer cells in terms of their relative ability to compete with [(3)H]oestradiol for binding to oestrogen receptor (ER), to induce a stably transfected oestrogen-responsive reporter gene (ERE-CAT) and to stimulate cell growth. In no case did sulphation abolish activity. The 4'-sulphation of genistein reduced oestrogen agonist activity to a small extent in whole-cell assays but increased the relative binding affinity to ER. The 7-sulphation of genistein, and also of equol, reduced oestrogen agonist activity substantially in all assays. By contrast, the position of monosulphation of daidzein acted in an opposing manner on oestrogen agonist activity. Sulphation at the 4'-position of daidzein resulted in a modest reduction in oestrogen agonist activity but sulphation of daidzein at the 7-position resulted in an increase in oestrogen agonist activity. Molecular modelling and docking studies suggested that the inverse effects of sulphation could be explained by the binding of daidzein into the ligand-binding domain of the ER in the opposite orientation compared with genistein and equol. This is the first report of sulphation enhancing activity of an isoflavone and inverse effects of sulphation between individual phytoestrogens.

The potential interactions between polyunsaturated fatty acids and colonic inflammatory processes.

n-3 Polyunsaturated fatty acids (PUFAs) are recognized as having an anti-inflammatory effect, which is initiated and propagated via a number of mechanisms involving the cells of the immune system. These include: eicosanoid profiles, membrane fluidity and lipid rafts, signal transduction, gene expression and antigen presentation. The wide-range of mechanisms of action of n-3 PUFAs offer a number of potential therapeutic tools with which to treat inflammatory diseases. In this review we discuss the molecular, animal model and clinical evidence for manipulation of the immune profile by n-3 PUFAs with respect to inflammatory bowel disease. In addition to providing a potential therapy for inflammatory bowel disease there is also recent evidence that abnormalities in fatty acid profiles, both in the plasma phospholipid membrane and in perinodal adipose tissue, may be a key component in the multi-factorial aetiology of inflammatory bowel disease. Such abnormalities are likely to be the result of a genetic susceptibility to the changing ratios of n-3 : n-6 fatty acids in the western diet. Evidence that the fatty acid components of perinodal adipose are fuelling the pro- or anti-inflammatory bias of the immune response is also reviewed.

Continuous PC6 wristband acupressure for relief of nausea and vomiting associated with acute myocardial infarction: a partially randomised, placebo-controlled trial.

OBJECTIVES: To assess the effectiveness of continuous PC6 acupressure as an adjunct to antiemetic drug therapy in the prevention and control of nausea and vomiting in the first 24h after myocardial infarction (MI). DESIGN: Partially randomised, partially blinded placebo-controlled, exploratory clinical study. SETTING: Coronary Care Unit, Torbay Hospital, Torquay, Devon. PARTICIPANTS: A total of 301 consecutive patients (205 males, 96 females) admitted following acute MI. INTERVENTION: The first 125 patients recruited received no additional intervention. Subsequent patients were randomised to receive either continuous PC6 acupressure or placebo acupressure. OUTCOME MEASURES: (1) Incidence of post-MI nausea and/or vomiting, (2) severity of symptoms, (3) use of antiemetic drugs, over 24h. RESULTS: There were no significant differences between the groups for the whole 24-h treatment period. However, the PC6 acupressure group experienced significantly lower incidence of nausea and/or vomiting during the last 20h (18%), compared with the placebo (32%) or control (43%) groups (P<0.05). The severity of symptoms and the need for antiemetic drugs were also reduced in the acupressure group, but these differences were not statistically significant. CONCLUSIONS: Continuous 24-h PC6 acupressure therapy as an adjunct to standard antiemetic medication for post-MI nausea and vomiting is feasible and is well accepted and tolerated by patients. In view of its benefits, further studies are worthwhile using earlier onset of treatment.

Legal preparedness for bioterrorism.

Responding to a terrorist biological weapon attack poses new challenges not only for the public health response community but also to the very construct of public health police powers as we know them today. States are debating the merits of revising and updating these powers in order to ensure an effective and legally appropriate response. This article covers three aspects of the policy debate: the experience in one state from a legislative perspective, a discussion from an academic viewpoint, and one example of the role of enhanced powers from the response perspective.

Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: synthesis and structure-activity relationships for 1-[N-(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes.

(2S)-2-(3-Chlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (1b) has been identified as a potent CCR5 antagonist having an IC50=10 nM. Herein, structure-activity relationship studies of non-spiro piperidines are described, which led to the discovery of 4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidine derivatives (3-5) as potent CCR5 antagonists.

The House of Lords report on complementary medicine: a summary.

The House of Lords Science and Technology Committee reviewed a large amount of oral and written evidence from a wide variety of sources in order to scrutinize CAM. In their published report, they propose that CAM be subdivided into three groups for operational purposes. They note that public satisfaction with CAM is high and use of CAM is increasing. Evidence is required that CAM has an effect above and beyond placebo, and once this is provided the public should have access to it and its potential benefits. Public interest is not protected by the current lack of regulation of CAM, which should be organized in an appropriate way by and for each therapy. Acupuncture and herbal medicine should be subject to statutory regulation, and possibly non-medical homeopathy. The regulatory status of herbal medicines is particularly unsatisfactory, and should be clarified and enforced in law. Training for CAM professionals should be standardized and independently accredited and, for many, should include basic biomedical science. Registered conventional health professionals should become more familiar with CAM. Research into CAM requires the same rigour as is required of conventional medicine, and recommendations are made as to how research could be encouraged, including pump-priming by the National Health Service and Medical Research Council. The provision of information to the public and health professionals is inadequate and recommendations are made on how this should be improved. Those working in the best regulated CAM professions should work towards integration with conventional medicine.

Effects of conjugated linoleic acid on the belly firmness and fatty acid composition of genetically lean pigs.

A study of the effects of conjugated linoleic acid (CLA) on the belly firmness and fatty acid composition of genetically lean pigs was conducted. From 75 to 120 kg live weight, 30 gilts were allowed ad libitum access to a corn-soybean meal diet supplemented with either 1% CLA oil (CLA-60) or 1% sunflower oil (SFO) or were fed the sunflower oil-supplemented diet restricted to the amount consumed by pigs fed the CLA-60 diet (RSFO). Conjugated linoleic acid oil consists of 60% positional and geometric isomers of CLA. Pigs fed SFO exhibited higher average daily gains (0.98 vs 0.80 kg/d, P < 0.01) than RSFO-fed pigs, but there were no effects of dietary treatment on feed intake or feed efficiency. Dietary treatment did not affect (P > 0.05) backfat thickness or longissimus muscle area. Bellies of gilts fed CLA-60 were subjectively evaluated to be firmer (2.91 vs 2.43 or 2.07 +/- 0.13, P < 0.01) than those of SFO- or RSFO-fed gilts, respectively. The longissimus muscle of gilts fed CLA-60 contained more saturated fatty acids (39.77 vs. 36.04 or 36.73 +/- 0.74%, P < 0.001) and less unsaturated fatty acids (60.23 vs 63.96 or 63.27 +/- 0.74%, P < 0.001) than that of gilts fed SFO or RSFO, respectively. The belly fat of gilts fed CLA-60 contained more saturated fatty acids (44.45 vs. 37.50 or 36.60 +/- 0.46%, P < 0.001) and less unsaturated fatty acids (54.78 vs. 61.75 or 62.47 +/- 0.46%, P < 0.001), resulting in lower iodine values (57.69 vs 66.37 or 65.62 +/- 0.91, P < 0.001) than that of gilts fed SFO or RSFO, respectively. Gilts fed CLA-60 accumulated more CLA in the longissimus muscle (0.55 vs 0.09 or 0.09 +/- 0.03%, P < 0.01) and belly fat (1.56 vs. 0.13 or 0.13 +/- 0.15%, P < 0.001) than did gilts fed SFO or RSFO, respectively. Dietary treatment did not affect (P > 0.05) 24-h pH, drip loss or subjective quality evaluations of the longissimus muscle. The effect of supplemental CLA to improve belly firmness is of practical significance and may provide a nutritional solution to carcass fat and belly firmness problems, thereby enhancing the overall value of extremely lean carcasses.

Applied kinesiology for treatment of women with mastalgia.

To determine whether an applied kinesiology technique was of benefit to women with breast pain, an open pilot study was conducted in which 88 newly presenting women with self-rated moderate or severe mastalgia were treated by applied kinesiology. This involved a hands-on technique consisting of rubbing a series of 'lymphatic reflex points' while touching painful areas of the breasts. The women were predominantly pre-menopausal, and patients with both cyclical and non-cyclical pain were included in the study. Patients' self-rated pain scores, both before and immediately after applied kinesiology were compared, together with a further score 2 months later. Immediately after treatment there was considerable reduction in breast pain in 60% of patients with complete resolution in 18%. At the visit after 2 months, there was a reduction in severity, duration and frequency of pain of 50% or more in about 60% of cases (P<0.0001). This preliminary study suggests that applied kinesiology may be an effective treatment for mastalgia, without side-effects and merits testing against standard drug therapies.

Mammary lipogenic enzyme activity, trans fatty acids and conjugated linoleic acids are altered in lactating dairy cows fed a milk fat-depressing diet.

The objectives of the present study were to examine the effect of a milk fat-depressing (MFD) diet on: 1) the activity of mammary acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), 2) ACC mRNA relative abundance and 3) distributions of conjugated linoleic acids (CLA) and trans-18:1 fatty acids (tFA) in milk fat. Twelve lactating Holstein cows were used in a single reversal design. Two diets were fed: a control diet (60:40% forage/concentrate) and an MFD diet (25:70% forage/concentrate, supplemented with 5% soybean oil). The MFD diet decreased (P: < 0 0.001) milk fat by 43% and ACC and FAS activity by 61 and 44%, respectively. A reduced ACC mRNA relative abundance (P: < 0.001) corresponded with the lower ACC activity. The fatty acids synthesized de novo were decreased (P: < 0. 002), whereas tFA were increased from 1.9 to 15.6% due predominantly to a change in trans-10-18:1 isomer (P: < 0.001). With the MFD diet, the trans-7, cis-9 and trans-10, cis-12 CLA isomers were elevated (P: < 0.001), in contrast to the decrease in trans-11-18:1 (P: < 0. 001) and cis-9, trans-11-18:2. The data were consistent with a dietary effect on mammary de novo FA synthesis mediated through a reduction in ACC and FAS activity and in ACC mRNA abundance. The results were compatible with a role of trans-10, cis-12 CLA in milk fat depression, but alterations noted in tFA and other CLA isomers suggest that they also may be important during diet-induced milk fat depression.

Phosphorylated morpholine acetal human neurokinin-1 receptor antagonists as water-soluble prodrugs.

The regioselective dibenzylphosphorylation of 2 followed by catalytic reduction in the presence of N-methyl-D-glucamine afforded 2-(S)-(1-(R)-(3, 5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(5-(2- phosphoryl-3-oxo-4H,-1,2,4-triazolo)methylmorpholine, bis(N-methyl-D-glucamine) salt, 11. Incubation of 11 in rat, dog, and human plasma and in human hepatic subcellular fractions in vitro indicated that conversion to 2 would be expected to occur in vivo most readily in humans during hepatic circulation. Conversion of 11 to 2 occurred rapidly in vivo in the rat and dog with the levels of 11 being undetectable within 5 min after 1 and 8 mg/kg doses iv in the rat and within 15 min after 0.5, 2, and 32 mg/kg doses iv in the dog. Compound 11 has a 10-fold lower affinity for the human NK-1 receptor as compared to 2, but it is functionally equivalent to 2 in preclinical models of NK-1-mediated inflammation in the guinea pig and cisplatin-induced emesis in the ferret, indicating that 11 acts as a prodrug of 2. Based in part on these data, 11 was identified as a novel, water-soluble prodrug of the clinical candidate 2 suitable for intravenous administration in humans.

Different standards for reporting ADRs to herbal remedies and conventional OTC medicines: face-to-face interviews with 515 users of herbal remedies.

AIMS: To determine whether adverse drug reactions (ADRs) to herbal remedies would be reported differently from similar ADRs to conventional over-the-counter (OTC) medicines by herbal-remedy users. METHODS: Face-to-face interviews (using a structured questionnaire) with 515 users of herbal remedies were conducted in six pharmacy stores and six healthfood stores in the UK. The questionnaire focused on the likely course of action taken by herbal-remedy users after experiencing an ADR associated with a conventional OTC medicine and a herbal remedy. RESULTS: Following a 'serious' suspected ADR, 156 respondents (30.3%) would consult their GP irrespective of whether the ADR was associated with the use of a herbal remedy or a conventional OTC medicine, whereas 221 respondents (42.9%) would not consult their GP for a serious ADR associated with either type of preparation. One hundred and thirty-four respondents (26.0%) would consult their GP for a serious ADR to a conventional OTC medicine, but not for a similar ADR to a herbal remedy, whereas four respondents (0.8%) would consult their GP for a serious ADR to a herbal remedy, but not for a similar ADR to a conventional OTC medicine. Similar differences were found in attitudes towards reporting 'minor' suspected ADRs. CONCLUSIONS: Consumers of herbal remedies would act differently with regard to reporting an ADR (serious or minor) to their GP depending on whether it was associated with a herbal remedy or a conventional OTC medicine. This has implications for herbal pharmacovigilance, particularly given the increasing use of OTC herbal remedies. The finding that a high proportion of respondents would not consult their GP or pharmacist following ADRs to conventional OTC medicines is also of concern.

Effect of a proprietary herbal medicine on the relief of chronic arthritic pain: a double-blind study.

Eighty-two subjects with chronic arthritic pain were randomly assigned for 2 months without cross-over to either Reumalex, a licenced over-the-counter (OTC) herbal medicine, or a placebo. Entry characteristics were determined by a previous survey of arthritic customers at pharmacy and healthfood shop outlets. The AIMS2 questionnaire was completed at monthly intervals throughout and for 2 months prior to the trial, and a modified Ritchie Index provided clinical scores. Subjects also completed diary recordings of their use of self-prescribed analgesics and events they considered significant. There was a small but statistically significant improvement in pain symptoms, less so in sufferers from osteoarthritis. There were no other significant changes in any other measures nor in the use of other self-prescribed analgesics. There were few side-effects noted. It is concluded that Reumalex has a mild analgesic effect in chronic arthritis at a level appropriate to self-medication.

HIV risk behavior, street outreach, and condom use in eight high-risk populations.

In this paper we examine risk behavior, exposure to street outreach, and condom use in samples of injecting drug users (IDUs) and high-risk youth. We used systematic sampling methods to produce representative samples of injecting drug users IDUs (five sites) and high-risk youth (three sites). The populations surveyed engaged in high levels of sexual risk behavior: 20% to 46% reported two or more sex partners in the last month. The majority (62% to 97%) knew someone infected with HIV. Condom use rates approached national health promotion goals for nonsteady partners but not for steady or main partners. Having a condom at time of interview was the most consistent predictor of condom use at last intercourse. Many of the respondents have been in contact with street outreach programs and many acknowledged some personal risk for HIV infection. However, most of the injecting drug users and high-risk youth interviewed (and their sex partners) were still at risk through unprotected sex.

PIP: Samples of IV drug users (IVDUs) and high-risk youth were surveyed to gain insight into their HIV risk behavior, exposure to street outreach, and condom use. The IVDUs were sampled from Atlanta, Philadelphia, Chicago, New York, and Los Angeles; 69-77% are male; they are predominantly Hispanic and Black; and more than 50% were older than age 40 years. The high-risk youth were sampled from Los Angeles, San Diego, New York, and San Francisco. They were aged 12-23 years and had been recurrently without shelter during the past year, or had been without permanent shelter for the past two months, or had derived their livelihood from dealing drugs on the street, prostitution, panhandling, and crime. 65-81% are male, approximately 50% in New York are White and 78% in San Francisco, 39-54% were age 20 or older, and 52-73% were currently living on the street, although only 10-32% had stayed in a shelter during the past year. At least 75% were supported at least in part by the street economy and 15-33% identified themselves as gay or bisexual. Many of the youth covered in the survey in San Francisco were on tour with the Grateful Dead folk rock music group. 20-46% reported having two or more sex partners in the last month, up to one-third reported having no sex partner in the past month, 62-97% knew someone infected with HIV, and 18-26% of the IVDUs and 11-41% of youth reported sometimes exchanging sex for money, food, shelter, or other things. Among respondents who had sex during the past month, 17-44% reported using a condom during vaginal sex with main partners, and 55-75% with other partners. The highest rates of condom use were for anal sex, followed by vaginal and oral sex. In most categories, however, the majority of respondents were not using condoms to protect themselves from HIV or other sexually transmitted diseases. Having a condom at the time of interview was the most consistent predictor of condom use at last intercourse. Many of the respondents had been in contact with street outreach programs and many acknowledged some personal risk for HIV infection.

A calbindin-immunoreactive cone bipolar cell type in the rabbit retina.

We have studied the distribution of the calcium-binding protein calbindin in the adult rabbit retina by using a commercially available antibody and immunocytochemical methods. The most heavily labeled cells are A-type horizontal cells, but B-type horizontal cells are also lightly labeled by this antibody. Among the horizontal cells, there is a mosaic of small, well-labeled somata, which we have identified as a subset of ON cone bipolar cells. In addition, some wide-field amacrine cells and a few large ganglion cells are also labeled for calbindin. The calbindin bipolar cells form a regular mosaic with a peak density of approximately 1,700 cells/mm2, falling to 550 cells/mm2 in the periphery. They account for about one-twelfth of cone bipolar cells, and they are narrowly stratified deep in sublamina 4 of the inner plexiform layer immediately above the rod bipolar terminals. Double-label experiments using an antibody to protein kinase C (PKC) indicate that the calbindin bipolar cells are completely distinct from the population of rod bipolar cells. Rod bipolar cells outnumber the calbindin cone bipolar cells by a factor of four to five. Further double-label experiments show that the calbindin bipolar cells are also labeled for recoverin. The calbindin bipolar cells are well coupled to AII amacrine cells, and they account for roughly 23% of the AII coupled bipolar cells. This suggests that there are three to four additional ON cone bipolar cell types that are coupled to AII amacrine cells. The calbindin cone bipolar cell described in this paper shares many characteristics with a reconstructed cone bipolar cell that forms the most gap junctions with AII amacrine cells (Strettoi et al. [1994] J. Comp. Neurol. 347:139-149). We conclude that these different methodologies provide complementary descriptions of the same cone bipolar cell type. The calbindin antibody defines a subset of cone bipolar cells in the rabbit retina. The cells in this subset are almost certainly the deepest of the cone bipolar cells. The tight stratification of the calbindin cone bipolar cell suggests that the inner plexiform layer is stratified according to depth, with narrow functional divisions within the broad partition of sublamina b, where ON signals are processed. The strength of coupling between the calbindin cone bipolar cells and AII amacrine cells suggests this pathway plays a major role under scotopic conditions.